There is an ongoing need in the art to improve high-speed methods and apparatuses to address the general need in the art for systematic, efficient, and economical material synthesis techniques as well as methods to analyze and to screen novel materials for useful properties. High-speed combinatorial methods often involve the use of array technologies that require rapid and accurate dispensing of fluids each having a precisely known chemical composition, concentration, stoichiometry, ratio of reagents, and/or volume. Such array technologies may be employed to carry out various synthetic processes and evaluations, particularly those that involve small quantities of fluids. For example, array technologies may employ large numbers of different fluids to form a plurality of reservoirs that, when arranged appropriately, create combinatorial libraries. Thus, array technologies are desirable because they are commonly associated with speed and compactness.
To carry out combinatorial techniques, a number of fluid dispensing techniques have been explored, such as pin spotting, pipetting, inkjet printing, and acoustic ejection. Many of these techniques possess inherent drawbacks that must be addressed, however, before the fluid dispensing accuracy required for the combinatorial methods can be achieved. For instance, a number of fluid dispensing systems are constructed using networks of tubing or other fluid-transporting vessels. Tubing, in particular, can entrap air bubbles, and nozzles may become clogged by lodged particulates. As a result, system failure may occur and cause spurious results. Furthermore, cross-contamination between the reservoirs of compound libraries may occur due to inadequate flushing of tubing and pipette tips between fluid transfer events. Cross-contamination can easily lead to inaccurate and misleading results.
Acoustic ejection provides a number of advantages over other fluid dispensing technologies. In contrast to inkjet devices, nozzleless fluid ejection devices are not subject to clogging and their associated disadvantages, e.g., misdirected fluid or improperly sized droplets. Furthermore, acoustic technology does not require the use of tubing or involve invasive mechanical actions, for example, those associated with the introduction of a pipette tip into a reservoir of fluid.
Acoustic ejection has been described in a number of patents. For example, U.S. Pat. No. 4,308,547 to Lovelady et al. describes a liquid droplet emitter that utilizes acoustic principles to eject droplets from a body of liquid onto a moving document to result in the formation of characters or barcodes thereon. A nozzleless inkjet printing apparatus is used such that controlled droplets of ink are propelled by an acoustical force produced by a curved transducer at or below the surface of the ink. Similarly, U.S. Pat. No. 6,666,541 to Ellson et al. describes a device for acoustically ejecting a plurality of fluid droplets toward discrete sites on a substrate surface for deposition thereon. The device includes an acoustic radiation generator that may be used to eject fluid droplets from a reservoir. Acoustic radiation may also be used to assess properties and spatial relationship associated with the fluid contained in the reservoir. Additional patents and patent documents that describe the use of acoustic radiation for ejection include U.S. Pat. No. 6,596,239 to Williams et al.
In general, nozzleless fluid ejection has been limited to ink printing applications. For example, U.S. Pat. No. 5,122,818 to Elrod et al. describes the use of acoustic radiation having simultaneous, broadband, and/or random frequency components to reduce focusing sensitivity in acoustic ink printers. In addition, droplet ejection involving the use of focused acoustic radiation has relied almost exclusively on lenses having F-numbers of approximately 1. Lenses having an F-number of 1 or less are limited to certain reservoir and fluid level geometries. For example, when lenses having an F-number of 1 are used, the surface of the fluid from which a droplet is ejected must be no further from the lens than the width of the lens aperture. In contrast, fluids for use in chemical, biochemical, bimolecular applications are often contained in individual wells of a well plate, wherein the wells each have aspect ratios of approximately 5:1. That is, the wells may be five times as deep as their diameter. Therefore, when an F1 lens is used in conjunction with a 5:1 aspect ratio well, acoustic ejection may be carried out by filling only the bottom fifth of the reservoir with fluid. Furthermore, lenses having low F-numbers provide relatively limited depth of focus. As a result, there is a greater sensitivity to the fluid level in the reservoir when using lower F-number lenses.
Nevertheless, a few of patents and publications have discussed droplet ejection using acoustic lenses having an F-number of 2 or greater. For example, Elrod et al. (1989), “Nozzleless droplet formation with focused acoustic beams,” J. Appl. Phys 65(9):3441-3447, teaches away from the use of acoustic lens having an F-number of 2 or greater by indicating that use of such lenses may yield unpredictable results in terms of droplet diameter and usable depth of focus. U.S. Pat. No. 6,416,164 to Stearns et al., however, teaches that lenses having a large F-number, e.g., F2 or greater, provides greater control over droplet size and velocity while enhancing depth of focus.
An increase in droplet ejection volume and/or velocity is generally associated with an increase in the power associated with the applied acoustic radiation. In some instances, an increased velocity is needed to ensure that the ejected droplet reaches an intended target. It has been observed, however, that an excessively high power level will tend to result in the ejection of secondary or “satellite” droplets. In addition, those secondary or satellite droplets formed using higher F-number lenses have properties that differ from those formed using a lower F-number lens.
In general, secondary or satellite droplet formation in the context of acoustic ejection is undesirable for a number of reasons. For example, when both primary and secondary droplets are formed by an upward application of focused acoustic radiation to a reservoir of fluid, the primary droplet may have sufficient velocity to reach a target whereas the secondary droplet may not. In such a circumstance, it may be necessary wait for the secondary droplet to return to the reservoir before ejecting a subsequent droplet. Otherwise, the secondary droplet may obstruct the trajectory of the subsequent droplet. In turn, droplet ejection rate is limited. Alternatively, a means may be needed to ensure that the secondary droplet does not obstruct the trajectory of the subsequently ejected droplet. However, this approach introduces additional complexity into any equipment used to carry out acoustic ejection.
Thus, there is a need in the art for improved methods and devices that are capable of carrying out nozzleless ejection using high-powered focused acoustic radiation without uncontrolled formation of satellite or secondary droplets.